Methods and apparatus for centrifugal liquid chromatography

Abstract

Apparatus and methods related to centrifugal liquid chromatography are described. An angular velocity can be simultaneously imparted to a large number of chromatographic enclosures. Via centrifugal forces, a mobile phase fluid including a sample can be driven through a stationary phase within the chromatographic enclosure to perform a chromatographic separation process on components of the sample. The use of centrifugation as a driving force can allow significantly smaller stationary phase particles to be employed as compared to high performance liquid chromatography (HPLC). Further, for an equivalent chromatographic separation process, the use of centrifugation can provide much greater separation efficiencies than HPLC.

1. A chromatographic system comprising:
 a rotor configured to rotate about an axis, said rotor comprising;
 an enclosed flow path configured to contain a fluid under pressure including 1) a first segment for receiving the fluid from an entrance to the flow path and communicating the fluid away from the axis and 2) a second segment in fluid communication with the first segment for communicating the fluid toward the axis and out an exit to the flow path, said exit located at a first radial distance from the axis, such that during a rotation of the rotor the fluid continually drains from the exit when a fluid level in the first segment is located at a second radial distance from the axis less than the first radial distance; and 
 a chromatographic enclosure, carried on the rotor, located between the entrance and the exit of the fluid conduit, said chromatographic enclosure being arranged to contain an associated chromatographic stationary phase and to facilitate transmission of a fluid through the chromatographic stationary phase contained within the chromatographic enclosure, wherein the fluid is driven through the chromatographic stationary phase via centrifugal force generated from the rotation of the rotor. 
 
 
     
     
       2. A chromatographic system as recited in  claim 1 , further comprising a flow conduit configured to receive the fluid exiting the chromatographic enclosure wherein the chromatographic enclosure is arranged to exit fluid away from the axis, the flow conduit configured to receive and turn the exiting fluid to allow the fluid to travel towards the axis. 
     
     
       3. A chromatographic system as recited in  claim 1 , wherein the chromatographic enclosure includes along its length a plurality of conduits through which fluid flows wherein each of the plurality of conduits provides a separate flow path through the chromatographic enclosure. 
     
     
       4. A chromatographic system as recited in  claim 1 , further comprising at least one mobile phase fluid reservoir in fluid communication with the chromatographic enclosure. 
     
     
       5. A chromatographic system as recited in  claim 4 , wherein the at least one mobile phase fluid reservoir is carried on the rotor. 
     
     
       6. A chromatographic system as recited in  claim 1 , further comprising a rotor drive system for imparting angular velocity to the rotor. 
     
     
       7. A chromatographic system as recited in  claim 1 , wherein a maximum operational pressure of the fluid in the enclosed flow path is less than 100 PSI. 
     
     
       8. A chromatographic system as recited in  claim 1 , wherein a particle diameter of the chromatographic stationary phase is less than approximately 1 micron. 
     
     
       9. A chromatographic system as recited in  claim 1 , wherein a particle diameter of the chromatographic stationary phase is between approximately 10 angstroms and 1 micron. 
     
     
       10. A chromatographic system as recited in  claim 1 , further comprising a sensor for detecting a leak of the fluid from the enclosed flow path carried on the rotor. 
     
     
       11. A chromatographic system as recited in  claim 1 , wherein the rotor includes a disk portion that extends substantially perpendicular to a center axis of rotation of the rotor and wherein a plurality of chromatographic enclosures are carried on the disk portion such that fluid in each of the chromatographic enclosures moves away from the center axis of rotation. 
     
     
       12. A chromatographic system as recited in  claim 1 , further comprising a coupling mechanism between a housing including the chromatographic enclosure and the rotor wherein the coupling mechanism allows an orientation of the chromatographic enclosure relative to the rotor to change from a first position when the chromatographic enclosure and the rotor are at rest to a second position when the chromatographic enclosure and the rotor are rotating. 
     
     
       13. A chromatographic system as recited in  claim 1 , wherein a portion of a fluid conduit carried on the rotor is flexible. 
     
     
       14. A chromatographic system as recited in  claim 1 , wherein the rotor includes a flow path that is split into multiple flow paths. 
     
     
       15. A chromatographic system as recited in  claim 1 , wherein the rotor includes multiple flow paths that coalesce into a single flow path downstream of the chromatographic enclosure. 
     
     
       16. A chromatographic system as recited in  claim 1 , further comprising one or more valves for controlling the fluid on the rotor and one or more electronically controllable actuation mechanisms for changing a state of the one or more valves. 
     
     
       17. A chromatographic system as recited in  claim 1 , further comprising one or more pumps for moving a fluid from one location to another location in the chromatographic system. 
     
     
       18. A chromatographic system as recited in  claim 17 , wherein the at least one pump is carried on the rotor. 
     
     
       19. A chromatographic system as recited in  claim 1 , further comprising a mobile phase fluid for use with the chromatographic stationary phase, said mobile phase fluid compatible with a chromatographic process wherein the chromatographic process includes one or more of reversed-phase partitioning, adsorption, anion exchange, cation exchange, size exclusion, gel filtration, affinity interactions or combinations thereof. 
     
     
       20. A chromatographic system as recited in  claim 1 , wherein the chromatographic enclosure comprises a cylindrical column having a length and an inner diameter. 
     
     
       21. A chromatographic system as recited in  claim 20 , wherein the length of the column is between 10 and 400 cm and the inner diameter is between 0.02 and 2000 mm. 
     
     
       22. A chromatographic system comprising:
 a rotor configured to rotate about an axis, said rotor comprising;
 a fluid conduit, having an internal area, an entrance and an exit located at a first radial distance from the axis, including 1) a first segment for receiving a fluid from the entrance and communicating the fluid away from the axis and 2) a second segment in fluid communication with the first segment for communicating the fluid toward the axis and out the exit such that during a rotation of the rotor the fluid continually drains from the exit when a fluid level in the first segment is at a second radial distance less than the first radial distance of the exit; 
 a chromatographic enclosure, carried on the rotor, located between the entrance and the exit of the fluid conduit, said chromatographic enclosure being arranged to contain an associated chromatographic stationary phase and to facilitate transmission of a fluid through the chromatographic stationary phase contained within the chromatographic enclosure, wherein the fluid is driven through the chromatographic stationary phase via centrifugal force generated from the rotation of the rotor. 
 
 
     
     
       23. A centrifugal chromatographic system as recited in  claim 22  further comprising a mixing chamber carried by the rotor and arranged to mix a mobile phase fluid with a sample fluid on the rotor to create the fluid, wherein the mixing chamber utilizes the rotation of a component carried by the rotor to enhance the mixing of the sample fluid with the mobile phase fluid, the mixing chamber being located upstream of the chromatographic enclosures. 
     
     
       24. A centrifugal chromatographic system as recited in  claim 23  further comprising a plurality of chromatographic enclosures wherein the mixing chamber is in fluid communication with each of the plurality of chromatographic enclosures. 
     
     
       25. A centrifugal chromatographic system as recited in  claim 22  further comprising a fluid reception mechanism configured to remain stationary and to receive, while the rotor is rotating, fluid exiting from the rotor that has passed through the chromatographic enclosure. 
     
     
       26. A centrifugal chromatographic system as recited in  claim 25  wherein the fluid reception mechanism is a fluid collection ring. 
     
     
       27. A centrifugal chromatographic system as recited in  claim 22  further comprising a fluid enclosure including a first portion configured to remain stationary while the rotor is rotating and a second portion, carried on the rotor, configured to rotate with the rotor wherein the fluid enclosure is in fluid communication with the chromatographic enclosure. 
     
     
       28. A centrifugal chromatographic system as recited in  claim 22  further comprising a fluid delivery mechanism in fluid communication with the chromatographic enclosure including one or more flow conduits configured to facilitate the delivery of a mobile phase fluid and/or a sample fluid to the chromatographic enclosure on the rotor while the rotor is rotating and the fluid delivery mechanism remains stationary such that approximately steady fluid flow conditions are established on the rotor. 
     
     
       29. A centrifugal chromatographic system as recited in  claim 22  further comprising a controller configured to determine whether a steady mobile phase fluid flow condition has been reached on the rotor; and a trigger a release of the sample fluid after it is determined that a steady mobile phase fluid flow condition has been reached.